Emilia Bagiella

Cardiac autonomic control buffers blood pressure variability responses to challenge: a psychophysiologic model of coronary artery disease.

This article presents a model that identifies effects of blood pressure variability (BPV) as a possible mechanism by which psychological/psychiatric factors and health behaviors confer increased risk of coronary artery disease (CAD) and acute coronary syndromes. Recent research in vascular biology and dynamics of coronary artery blood flow suggests that BPV may have pathogenic effects on the coronary endothelium, plaque formation, and plaque stability. Thus, BPV may be a risk factor for cardiovascular disease independent of mean arterial pressure. The model proposes that autonomic control of the heart exerts a buffering or inhibitory influence on oscillations in blood pressure. Established psychological/behavioral risk factors for CAD, such as depression, hostility, and anxiety, as well as physical deconditioning and aging, are associated with diminished autonomic control of the heart, which may disinhibit pathogenic BPV. Together, these data suggest a coherent, testable psychophysiological model of CAD. In this article, we review these data and make recommendations for research to examine the model.

A PROSPECTIVE ANALYSIS OF TIME TO NORMALIZATION OF SERUM TESTOSTERONE AFTER WITHDRAWAL OF ANDROGEN DEPRIVATION THERAPY

PURPOSEnPatients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent androgen deprivation therapy. Prostate specific antigen (PSA) is altered during androgen deprivation therapy, and as a result the prognostic significance and accuracy of PSA values measured before serum testosterone has normalized are questionable because the patient is still effectively on androgen deprivation therapy. We determine the time it takes for serum testosterone to return to normal after withdrawal of androgen deprivation therapy.nnnMATERIALS AND METHODSnSerial serum testosterone was prospectively measured at 3-month intervals in 68 men after withdrawal of androgen deprivation therapy. The number of months to return to normal serum testosterone 270 ng./dl. or greater, was calculated for each patient. Patients were stratified according to duration of androgen deprivation, age and type of luteinizing hormone releasing hormone agonist used.nnnRESULTSnMedian patient age was 71 years (range 46 to 88). Median time to normalization of testosterone was 7 months (range 1 to 58). At 3, 6 and 12 months 28%, 48% and 74% of men had normal serum testosterone, respectively. Serum testosterone took significantly longer to return to normal in patients on androgen deprivation therapy for 24 months or greater compared to those on therapy for less than 24 months (log-rank p = 0.0034). There was no statistical significance based on age or type of luteinizing hormone releasing hormone agonist used.nnnCONCLUSIONSnAndrogen deprivation has an effect on serum testosterone that extends beyond the cessation of treatment. Serum testosterone should be measured in all men until normalization. These results should be applied to the interpretation of PSA levels after withdrawal of androgen deprivation therapy. In addition, these data have implications regarding dose scheduling and definition of biochemical (PSA) failure after primary therapy.

Supratentorial Ependymomas in Adult Patients

OBJECTIVEnEpendymomas arise from different areas in the neuraxis and have variable outcomes that depend on tumor location and patient age at the time of presentation. The predictive value of histology for these tumors is unresolved. We report a series of adult patients with supratentorial ependymomas to characterize the roles of surgery, histology, ploidy, and proliferation index in tumor control.nnnMETHODSnFourteen of the 23 supratentorial ependymomas were in the region of the third ventricle and the remainder were located in the hemispheres. Resections were gross total in 12 patients, subtotal in 8, and biopsy in 3. A single pathologist reviewed all slides and quantitated the deoxyribonucleic acid. The mean follow-up duration was 95 months (+/-75 mo).nnnRESULTSnAll of the malignant ependymomas were hemispheric (n = 4). Mortality occurred only in patients with third ventricular tumors; two patients died as a result of surgical complications and three as a result of tumor progression. Kaplan-Meier estimates of 5- and 10-year survival rates were 100% for hemispheric and 72.5% for third ventricular tumors (62.5% including the two perioperative deaths). The median time to recurrence was 53 months, with a 10-year progression-free survival rate of 27%. Univariate analysis revealed that recurrence was associated with malignant histology, including mitoses, cellularity, and aneuploidy. For nonmalignant ependymomas, recurrence was associated with subtotal resection and metastases. S-phase fraction did not correlate with recurrence. Only malignant histology correlated with recurrence on multivariate analysis.nnnCONCLUSIONnAlthough the numbers are too small to draw any definite conclusions, treatment of ependymomas that arise in the supratentorial compartment in adult patients results in excellent outcomes despite frequent recurrences. Association with the third ventricle and metastases seem to have a negative impact on survival, whereas malignant histology, subtotal resection, and metastases may be predictors of recurrence.

Relationships between circulating catecholamines and low frequency heart period variability as indices of cardiac sympathetic activity during mental stress.

Heart rate increases during psychological stress are the product of cardiac sympathetic activation and parasympathetic withdrawal.Levels of plasma epinephrine (E) and norepinephrine (NE) have a long history as indicators of cardiac adrenergic activity and, accordingly, generally increase in response to psychological challenge. Recently, several investigators have suggested that indices derived from power spectral analysis of heart period variability (HPV) also may provide estimates of cardiac sympathetic nervous system activity. These indices include power in the low frequency band (0.04-0.15 Hz, LF), and the ratio of low to high frequency (0.15-0.50 Hz, HF) power (LF/HF). The relationship between spectral and neurohumoral indices during psychological stress has not been investigated. This issue was addressed by studying spectrally defined measures of HPV and levels of plasma E and NE in 34 normal subjects who participated in a study of responsiveness to a psychologically challenging arithmetic task.Heart rate (HR), LF and HF power, the LF/HF ratio, and blood pressure were measured during the 5-minute baseline and 5-minute task periods. Integrated samples of forearm venous blood were collected for both periods. E and NE were analyzed by high performance liquid chromatography. The task produced significant increases in HR, systolic and diastolic pressures, and NE. Of the 12 Pearson correlation coefficients used to examine the relationships between power spectral measures and catecholamines for the baseline, task, and delta values, none achieved statistical significance, suggesting little relationship between neurohumoral and spectral estimates of cardiac sympathetic activity. We conclude that under conditions of psychological stress, LF power provides no useful information about cardiac sympathetic activity, both because power in this frequency band falls whereas HR rises and because there is no relationship between LF power and plasma NE.

DECLINING SPERM COUNTS IN THE UNITED STATES? A CRITICAL REVIEW

PURPOSEnRecent reports suggest declining sperm counts in the United States. These reports did not include all available data and did not account for geographic variations noted in prior studies. We examined all available data on U.S. sperm counts and evaluated whether geographic variations account for the decline suggested.nnnMATERIALS AND METHODSnWe reviewed all 29 U.S. studies from 1938 to 1996 reporting manually counted semen analyses of 9,612 fertile or presumably fertile men. We determined mean sperm concentrations by geographic location with weighted analysis of variance, and assessed any changes with time by linear regression analysis.nnnRESULTSnMean sperm concentrations from New York were significantly higher than from all other U.S. cities (98.6 versus 71.6 x 10(6) sperm per cc, respectively, p = 0.006). There has been no statistically significant change with time for mean sperm concentrations reported from New York (p = 0.49) or from U.S. cities other than New York (p = 0.62). Analysis without separating by location revealed a decline (p = 0.047).nnnCONCLUSIONSnSperm concentrations are highest in New York compared to other U.S. cities. When accounting for this geographic difference and examining all available data, there appears to be no significant change in sperm counts in the U.S. during the last 60 years. Further studies addressing the causes of geographic variations are needed.

DEXAMETHASONE DOES NOT SIGNIFICANTLY CONTRIBUTE TO THE RESPONSE RATE OF DOCETAXEL AND ESTRAMUSTINE IN ANDROGEN INDEPENDENT PROSTATE CANCER

PURPOSEnWe evaluated the independent response rate of dexamethasone before docetaxel and estramustine administration as measured by changes in serum prostate specific antigen (PSA) in patients with androgen independent prostate cancer.nnnMATERIALS AND METHODSnA total of 12 patients received 20 mg. dexamethasone orally every 6 hours for 3 doses repeated every 3 weeks before starting cytotoxic therapy with estramustine and docetaxel. After progression on dexamethasone 280 mg. estramustine orally 3 times daily on days 1 to 5 and 70 mg./m.2 docetaxel intravenously for 1 hour on day 2 were given.nnnRESULTSnNone of the patients initially treated with dexamethasone monotherapy (median 1 cycle, range 1 to 5) had a PSA decline of 50% or greater. Median PSA increase on monotherapy was 47% (range 0% to 22%). On estramustine and docetaxel therapy PSA decreased 50% or greater in 11 patients (92%, 95% confidence intervals [CI] 60 to 99) and 80% or greater in 7 (58%, 95% CI 29 to 84), and normalized in 5 (42%, 95% CI 16 to 71), with a median duration of response of 153 (range 42 to 371), 132 (range 84 to 287) and 84 (range 21 to 174) days, respectively. Median times to reach 50% and 80% decreases in baseline PSA were 21 (range 21 to 209) and 63 (range 21 to 138) days, respectively. In 9 patients (75%, 95% CI 43 to 93) PSA decreased at least 50% by week 9. Of 4 patients with bidimensionally measurable disease 3 had a partial response. Median time to progression was 263 days (range 91 to 378).nnnCONCLUSIONSnAdministration of 20. mg. dexamethasone orally every 6 hours for 3 doses every 3 weeks does not significantly contribute to the PSA response rate of estramustine and docetaxel.

Brief interval heart period variability by different methods of analysis correlates highly with 24 h analyses in normals

Heart period variability (HPV) measured from 24 h ECG recordings predicts mortality following myocardial infarction and may be a measure of cardiovascular health in the general population. Since epidemiologic evaluation of healthy people will require alternatives less intensive than 24 h recording, we investigated the relationship between HPV derived from 24 h and 5 min recordings, using two approaches for obtaining RR intervals. Template-matching (TM) algorithms were applied to 24 h ECG recordings from 41 normal subjects (mean age 35.7 +/- 13 years). Five min of ECG data during this 24 h period also were collected by an on-line microcomputer-based system for peak detection (PD) analysis. Intraclass correlations comparing the TM and PD approaches on the 5 min period were .80 or greater for all measures of HPV. Pearson correlation coefficients between the 5 min (TM) estimates and 24 h data and 5 min (PD) estimates and 24 h data exceeded .60 and .55, respectively, for all but one variable, with all p values < .05. Thus, in healthy adults, TM and PD approaches to HPV estimation from short segments of ECG data are highly consistent and the correlations between HPV obtained from brief intervals and 24 h measures were substantial, suggesting that assessment of HPV as a screening measure of cardiac autonomic control in healthy adults may be feasible.

Physiologic responses to cognitive challenge during pregnancy: effects of task and repeat testing

Physiological responses to stress during pregnancy are believed to influence birth outcomes. Researchers have studied pregnant women in laboratory stressor paradigms to investigate these associations, yet normative data on cardiovascular and respiratory responses to laboratory challenge during pregnancy are not yet established. To begin to establish such normative data, this study examined the effects of task and repeat stressor exposure on reactivity in third-trimester pregnant women. Thirty-one healthy pregnant women (mean age=27 years; range 18-36) between the 33rd and 39th week of pregnancy, were instrumented for continuous electrocardiography, blood pressure (BP), and respiration data. Subjects rested quietly for a 5-min baseline and then performed both a mental arithmetic stressor and a Stroop color-word-matching task, each 5 min in length and each followed by a 5-min recovery period. The order of the tasks was counterbalanced. After each 5-min period, subjects rated the period on a 10-point stress scale. Averaged across task type and challenge period, systolic and diastolic BP and respiration rate increased significantly in response to cognitive challenge, but heart rate (HR) did not. When data were examined for task and period effects, the following results emerged: the Stroop task elicited significantly greater systolic BP and HR reactivity than the arithmetic task, yet subjects rated the arithmetic task as more stressful. Averaged across task type, subjects showed greater systolic BP reactivity during the second challenge period compared to the first. Finally, womens BP tended to drift upward and did not return to baseline during the first recovery period. These findings indicate that averaging data across tasks and periods can obscure the time course of response patterns that may be important in the study of associations between maternal stress and perinatal development, as well as in other research on reactivity to repeat stress exposure.